Myeloperoxidase to Risk Stratify Emergency Department Patients with Chest Pain

Previous studies suggest that serum myeloperoxidase (MPO) is a potentially useful biomarker to risk stratify troponin-negative patients with suspected myocardial ischemia. We hypothesized that the relationship between initial serum MPO levels would correlate with 30-day adverse cardiac outcomes for low risk emergency department (ED) patients with suspected myocardial ischemia. This prospective cohort study enrolled ED patients with chest pain or suspected myocardial ischemia, non-diagnostic ECG, and initially negative cardiac troponin I. We defined 30-day adverse cardiac events as death, myocardial infarction, or coronary revascularization. We calculated summary statistics, standard deviation (SD), odds ratios (OR), 95% confidence intervals (CI), and receiver operating characteristics (ROC). We enrolled 159 patients who had a mean age of 55 ± 13, were 56% female, of whom 5.2% suffered at least one adverse cardiac event. MPO test characteristics were poor, with an ROC area of only 0.47 (CI 0.23-0.71). MPO levels were not associated with adverse events (OR 0.99, CI 0.98-1.01, p=0.62). The optimal ROC cutpoint to predict adverse cardiac events had poor sensitivity and specificity (57% and 52%, respectively). Mean MPO concentrations in the event group did not differ from the non-event group. In this limited cohort of low risk ED patients with chest pain, we were unable to demonstrate utility of MPO for risk stratification. If confirmed in larger studies, these findings may call into question the routine use of MPO for low-risk chest pain

Ultrafast laser-writing of liquid crystal waveguides

With the development of conformable photonic platforms, particularly those that could be interfaced with the human body or integrated into wearable technology, there is an ever increasing need for mechanically flexible optical photonic elements in soft materials. Here, we realize mechanically flexible liquid crystal (LC) waveguides using a combination ultrafast direct laser writing and ultraviolet (UV) photo-polymerization. Results are presented that demonstrate that these laser-written waveguides can be either electrically switchable (by omitting the bulk UV polymerization step) or mechanically flexible. Characteristics of the waveguide are investigated for different fabrication conditions and geometrical configurations, including the dimensions of the waveguide and laser writing power. Our findings reveal that smaller waveguide geometries result in reduced intensity attenuation. Specifically, for a 10 μm wide laser written channel in a 14 μm-thick LC layer, a loss factor of -1.8 dB/mm at λ = 650 nm was observed. Following the UV polymerization step and subsequent delamination of the glass substrates, we demonstrate a free-standing flexible LC waveguide, which retains waveguide functionality even when bent, making it potentially suitable for on-skin sensors and other photonic devices that could interface with the human body. For the flexible LC waveguides fabricated in this study, the loss in a straight waveguide with a cross-sectional area of 20 μm × 20 μm was recorded to be -0.2 dB/mm. These results highlight the promising potential of electrically-responsive and mechanically moldable optical waveguides using laser writing and UV-assisted polymer network formation

Variation in the use of observation status evaluation in Massachusetts acute care hospitals, 2003–2006

Background Observation evaluation is an alternate pathway to inpatient admission following Emergency Department (ED) assessment. Aims We aimed to describe the variation in observation use and charges between acute care hospitals in Massachusetts from 2003 to 2006. Methods Retrospective pilot analysis of hospital administrative data. Patients discharged from a Massachusetts hospital between 2003 and 2006 after an observation visit or inpatient hospitalization for six emergency medical conditions, grouped by the Clinical Classification System (CCS), were included. Patients discharged with a primary obstetric condition were excluded. The primary outcome measure, “Observation Proportion ” (pOBS), was the use of observation evaluation relative to inpatient evaluation (pOBS = n Observation/(n Observation + n Inpatient). We calculated pOBS, descriptive statistics of use and charges by the hospital for each condition. Results From 2003 to 2006 the number of observation visits in Massachusetts increased 3.9 % [95 % confidence interval (CI) 3.8 % to 4.0%] from 128,825 to 133,859, while inpatient hospitalization increased 1.29 % (95 % CI 1.26 % to 1.31%) from 832,415 to 843,617. Nonspecific chest pain (CCS 102) was the most frequently observed condition with 85,843 (16.3 % of total) observation evaluations. Observation visits for nonspecific chest pain increased 43.5 % from 2003 to 2006. Relative observation utilization (pOBS) for nonspecific chest pain ranged from 25 % to 95% across hospitals. Wide variation in hospital use of observation and charges was seen for all six emergency medical conditions. Conclusions There was wide variation in use of observation across six common emergency conditions in Massachusetts in this pilot analysis. This variation may have a substantial impact on hospital resource utilization. Further investigation into the patient, provider and hospital-level characteristics that explain the variation in observation use could help improve hospital efficiency

Introduction of a novel magnetic resonance imaging-based scoring system for assessing disease activity in children with juvenile dermatomyositis

Objectives: We aimed to develop and assess the reliability of a novel MRI-based scoring system for reporting the severity of MRI findings in children with suspected JDM. Methods: Nine consultant paediatric radiologists independently assessed and scored 40 axial and 30 coronal thigh MR images of children with suspected JDM on two occasions using the juvenile dermatomyositis magnetic resonance Imaging Score (JIS). JIS was calculated for both reads for each plane and each limb, with possible scores ranging from 0 (normal) to 100 (severe). Inter- and intraobserver agreement was calculated using the intraclass correlation coefficient (ICC) and two- and one-way random effects models, respectively. Bland-Altman plots of the difference in JIS against the average JIS were also produced for each rater. Results: Overall, the interobserver reliability and agreement was good-for axial images, JIS ranged from 46.8 to 61.0 [ICC = 0.88 (95% CI: 0.82, 0.92)] for the left limb and 47.9-61.4 [ICC = 0.87 (95% CI: 0.81, 0.92)] for the right limb. For coronal images, JIS ranged from 56.7 to 65.1 [ICC = 0.90 (95% CI: 0.85, 0.95)] for the left limb and 55.7 to 66.8 [ICC = 0.90 (95% CI: 0.84, 0.94)] for the right limb. The intraobserver reliability and agreement was good, with ICC ranging from 0.90 to 0.94. Conclusion: JIS is a semi-objective scoring system with potential to serve as a reliable biomarker of disease severity and response to therapeutic interventions in children with JDM

Oncogenic PIK3CA Mutations Reprogram Glutamine Metabolism in Colorectal Cancer

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations

Oncogenic PIK3CA Mutations Reprogram Glutamine Metabolism in Colorectal Cancer

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe